Charlotte A. Huber

In high-income countries, degenerative diseases are the primary cause of death

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is routinely used for bacterial identification. It would be highly beneficial to also be able to use the technology as a fast way to detect clinically relevant clones of bacterial species. However, studies to this aim have often had limited success. The methods used for data acquisition, processing and data interpretation are highly diverse amongst studies on MALDI-TOF MS sub-species typing. In addition to this, feasibility may depend on the bacterial species and strains investigated, making it difficult to determine what methods may or may not work. In our paper, we have reviewed recent research on MALDI-TOF MS typing of bacterial strains. Although we found a lot of variation amongst the methods used, there were approaches shared by multiple research groups. Multiple spectra of the same isolate were often combined before further analysis for strain distinction. Many groups used a protein extraction step to increase resolution in their MALDI-TOF MS results. Peaks at a high mass range were often excluded for data interpretation. Three groups have found ways to determine feasibility of MALDI-TOF MS typing for their set of strains at an early stage of their project.

Clostridium difficile infection (CDI) is becoming less exclusively a healthcare-associated (HA) infection. Community-associated (CA)-CDI has increased over the past decades. It has been postulated that asymptomatic toxigenic C. difficile (TCD)-colonised patients may play a role in the transfer of C. difficile between the hospital setting and the community. Thus, to investigate the relatedness of C. difficile across the hospital and community settings, we compared host and pathogen characteristics among symptomatic and asymptomatic patients in these two settings over a 3-year period. Two studies were simultaneously conducted, the first study enrolled symptomatic CDI patients from two tertiary hospitals and the community in two Australian states; while the second study enrolled asymptomatic TCD-colonised patients from the same tertiary hospitals. A total of 324 patients (96 HA-CDI, 152 CA-CDI and 76 TCD-colonised) were enrolled. The predominant C. difficile ribotypes isolated in the hospital setting corresponded with those isolated in the community, 79% of the C. difficile isolates from the hospitals had a matching ribotype isolated from the community, suggesting that transmission between these two settings is occurring. Toxigenic C. difficile strains causing symptomatic infection were similar to those causing asymptomatic infection and patients exposed to antimicrobials prior to admission were more likely to develop symptomatic infection (OR 2.94; 95%CI 1.20-7.14). Our findings suggest that development of CDI symptoms in a setting without establishment of hospital epidemics with binary toxin producing C. difficile strains may be driven mainly by host susceptibility and exposure to antimicrobials, rather than by C. difficile strain characteristics.

The epidemiology of Clostridium difficile infection (CDI) has changed over the past decades with the emergence of highly virulent strains. The role of asymptomatic C. difficile colonization as part of the clinical spectrum of CDI is complex because many risk factors are common to both disease and asymptomatic states. In this article, we review the role of asymptomatic C. difficile colonization in the progression to symptomatic CDI, describe the epidemiology of asymptomatic C. difficile colonization, assess the effectiveness of screening and intensive infection control practices for patients at risk of asymptomatic C. difficile colonization, and discuss the implications for clinical practice. A narrative review was performed in PubMed for articles published from January 1980 to February 2015 using search terms ‘Clostridium difficile’ and ‘colonization’ or ‘colonisation’ or ‘carriage’. There is no clear definition for asymptomatic CDI and the terms carriage and colonization are often used interchangeably. The prevalence of asymptomatic C. difficile colonization varies depending on a number of host, pathogen, and environmental factors; current estimates of asymptomatic colonization may be underestimated as stool culture is not practical in a clinical setting. Asymptomatic C. difficile colonization presents challenging concepts in the overall picture of this disease and its management. Individuals who are colonized by the organism may acquire protection from progression to disease, however they also have the potential to contribute to transmission in healthcare settings.

Objectives The objective of this study was to determine the activity of fidaxomicin and comparator antimicrobials against Clostridium difficile isolated from patients with C. difficile infection (CDI) in Australian hospitals and in the community. Methods One private and one public laboratory from five states in Australia submitted a total of 474 isolates/PCR-positive stool samples during three collection periods in August–September 2013 (n = 175), February–March 2014 (n = 134) and August–September 2014 (n = 165). Isolate identification was confirmed by selective culture for C. difficile and a proportion of isolates from each state were characterized by PCR for toxin genes and PCR ribotyping. MICs of fidaxomicin and eight comparator antimicrobials were determined for all isolates using agar methodology. Results Site collection yielded 440 isolates of C. difficile and PCR revealed a heterogeneous strain population comprising 37 different PCR ribotypes (RTs), 95% of which were positive for tcdA and tcdB (A+B+). The most common RTs were 014 (29.8%) and 002 (15.9%). Epidemic RT 027 was not identified; however, small numbers of virulent RTs 078 and 244 were found. Resistance to vancomycin, metronidazole and fidaxomicin was not detected and resistance to moxifloxacin was very low (3.4%). Fidaxomicin showed potent in vitro activity against all 440 isolates (MIC₅₀/MIC₉₀ 0.03/0.12 mg/L) and was superior to metronidazole (MIC₅₀/MIC₉₀ 0.25/0.5 mg/L) and vancomycin (MIC₅₀/MIC₉₀ 1/2 mg/L). Conclusions These data confirm the potent in vitro activity of fidaxomicin against C. difficile. Moreover, this study provides an important baseline for ongoing long-term surveillance of antimicrobial resistance and prospective tracking of prominent and emerging strain types.